Aberrant striatal dopamine transmitter dynamics in brain-derived neurotrophic factor-deficient mice

• Published in: Journal of neurochemistry Vol. 120; no. 3; pp. 385 - 395
• Main Authors: Bosse, Kelly E., Maina, Francis K., Birbeck, Johnna A., France, Marion M., Roberts, Joseph J. P., Colombo, Michelle L., Mathews, Tiffany A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-02-2012; Wiley-Blackwell
• Subjects: 3,4-Dihydroxyphenylacetic Acid - metabolism; Animals; Biochemistry and metabolism; Biological and medical sciences; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - deficiency; Brain-Derived Neurotrophic Factor - pharmacology; Caudate-putamen; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Chromatography, Liquid; Corpus Striatum - cytology; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine; Dopamine - metabolism; dopamine transporter; Electric Stimulation; Electrochemical Techniques; Extracellular Fluid - drug effects; Extracellular Fluid - metabolism; Extracellular levels; fast scan cyclic voltammetry; Forebrain; Fundamental and applied biological sciences. Psychology; Homeostasis; Homeostasis - drug effects; Homeostasis - genetics; Homovanillic Acid - metabolism; l-DOPA; Levodopa; Levodopa - metabolism; Linear Models; Locomotor activity; Mental disorders; Metabolites; Mice; Mice, Knockout; Microdialysis; Motor Activity - genetics; Neostriatum; Neurons; Neurotransmission; Neurotransmitters; Potassium; Potassium Chloride - pharmacology; Rodents; Synaptic transmission; Time Factors; Vertebrates: nervous system and sense organs; Dopamine; Rodentia; Central nervous system; Basal ganglion; Corpus striatum; Catecholamine; Extracellular; Putamen; Encephalon; Cyclic voltammetry; Vertebrata; Mammalia; Endogenous; Microdialysis; dopamine transporter; Mouse; Dynamics; Synaptic transmission; fast scan cyclic voltammetry; Neurotransmitter; Dopaminergic neuron; locomotor activity; DOPA; Potassium
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2011.07531.x

J. Neurochem. (2012) 120, 385–395.
Brain‐derived neurotrophic factor (BDNF) modulates the synaptic transmission of several monoaminergic neuronal systems, including forebrain dopamine‐containing neurons. Recent evidence shows a strong correlation between neuropsychiatric disorders and BDNF hypofunction. The aim of the present study was to characterize the effect of low endogenous levels of BDNF on dopamine system function in the caudate‐putamen using heterozygous BDNF (BDNF+/−) mice. Apparent extracellular dopamine levels in the caudate‐putamen, determined by quantitative microdialysis, were significantly elevated in BDNF+/− mice compared with wildtype controls (12 vs. 5 nM, respectively). BDNF+/− mice also had a potentiated increase in dopamine levels following potassium (120 mM)‐stimulation (10‐fold) relative to wildtype controls (6‐fold). Slice fast‐scan cyclic voltammetry revealed that BDNF+/− mice had reductions in both electrically evoked dopamine release and dopamine uptake rates in the caudate‐putamen. Superfusion of BDNF led to partial recovery of the electrically stimulated dopamine release response in BDNF+/− mice. Conversely, tissue accumulation of L‐3,4‐dihydroxyphenylalanine, extracellular levels of dopamine metabolites, and spontaneous locomotor activity were unaltered. Together, this study indicates that endogenous BDNF influences dopamine system homeostasis by regulating the release and uptake dynamics of pre‐synaptic dopamine transmission.
Endogenous BDNF influences dopamine system homeostasis. The effect of low endogenous levels of brain‐derived neurotrophic factor (BDNF) on dopamine system function was characterized in the caudate‐putamen of heterozygous BDNF (BDNF+/−) mice. BDNF+/− mice had significantly elevated basal and potassium‐stimulated extracellular dialysate dopamine levels compared to wildtype mice. Endogenous BDNF influences dopamine system homeostasis by regulating the release and uptake dynamics of pre‐synaptic dopamine transmission as measured by voltammetry.